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Title: Associations between long-term exposure to PM2.5 component species and blood DNA methylation age in the elderly: The VA normative aging study.

Authors: Nwanaji-Enwerem, Jamaji C; Dai, Lingzhen; Colicino, Elena; Oulhote, Youssef; Di, Qian; Kloog, Itai; Just, Allan C; Hou, Lifang; Vokonas, Pantel; Baccarelli, Andrea A; Weisskopf, Marc G; Schwartz, Joel D

Published In Environ Int, (2017 May)

Abstract: BACKGROUND: Long-term PM2.5 exposure and aging have been implicated in multiple shared diseases; studying their relationship is a promising strategy to further understand the adverse impact of PM2.5 on human health. OBJECTIVE: We assessed the relationship of major PM2.5 component species (ammonium, elemental carbon, organic carbon, nitrate, and sulfate) with Horvath and Hannum DNA methylation (DNAm) age, two DNA methylation-based predictors of chronological age. METHODS: This analysis included 552 participants from the Normative Aging Study with multiple visits between 2000 and 2011 (n=940 visits). We estimated 1-year PM2.5 species levels at participants' addresses using the GEOS-chem transport model. Blood DNAm-age was calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. We fit linear mixed-effects models, controlling for PM2.5 mass and lifestyle/environmental factors as fixed effects, with the adaptive LASSO penalty to identify PM2.5 species associated with DNAm-age. RESULTS: Sulfate and ammonium were selected by the LASSO in the Horvath DNAm-age models. In a fully-adjusted multiple-species model, interquartile range increases in both 1-year sulfate (95%CI: 0.28, 0.74, P<0.0001) and ammonium (95%CI: 0.02, 0.70, P=0.04) levels were associated with at least a 0.36-year increase in Horvath DNAm-age. No PM2.5 species were selected by the LASSO in the Hannum DNAm-age models. Our findings persisted in sensitivity analyses including only visits with 1-year PM2.5 levels within US EPA national ambient air quality standards. CONCLUSION: Our results demonstrate that sulfate and ammonium were most associated with Horvath DNAm-age and suggest that DNAm-age measures differ in their sensitivity to ambient particle exposures and potentially disease.

PubMed ID: 28284819 Exiting the NIEHS site

MeSH Terms: Aged; Aging/blood*; Aging/genetics; Air Pollutants/analysis*; Air Pollutants/toxicity; DNA Methylation/drug effects*; DNA/blood*; Environmental Monitoring/methods*; Female; Humans; Inhalation Exposure/analysis; Male; Particle Size; Particulate Matter/analysis*; Particulate Matter/toxicity; United States; United States Environmental Protection Agency

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